We intend to study the activity of hepatic monooxygenases in the elderly. As marker for the activity of hepatic monooxygenases in the baseline state and after induction or inhibition of drug metabolism we will measure the urinary excretion of 6Beta-hydroxycortisol (6Beta0HF). 6Beta0HF is a major urinary cortisol metabolilte formed primarily in the endoplasmic reticulum of hepatocytes. This metabolite is the major unconjugated urinary product of cortisol. We and others have shown that 6Beta0HF excretion is a sensitive, non-invasive indicator of hepatic microsomal enzyme induction and possibly also inhibition in children and adults. The same cytochrome P-450 dependent oxidase systems that hydroxylate various drugs are probably also responsible for the 6Beta-hydroxylation of cortisol. Because 6BOHF excretion varies with changes in adrenal secretion of cortisol ratios of 6BetaOHF to urinary free cortisol (FF) will be calculated. The 6Beta0HF ratio shows no circadian change and is stable in a given individual. Thus random measurements of 6Beta0HF/FF are useful to detect enzyme inducation or inhibition. Activity of hepatic monooxygenases may be altered in the elderly. We will establish: 1) normative data for the excretion of 6Beta0HF in the aged adult. 2) evaluate age-related changes in induction or inhibition of mixed function oxidases measuring the change in 6Beta0HF excretion after therapeutically administered drugs. Age-related changes do occur in the elderly and age-related changes in drug metabolizing capacity are of clinical relevance. Induction and inhibition of drug metabolism in the aged adult is altered and may interfere with drug disposition. This is the first non-invasive approach to identify and quantify changes in drug metabolizing activity that may be associated with old age.